Tranexamic Acid with Intensive Blood Pressure Management in Ultra-Early Intracerebral Hemorrhage (TIME-ICH)

Safety and Efficacy of Intravenous Tranexamic Acid with Intensive Blood Pressure Management in Ultra-Early Intracerebral Hemorrhage

This is a prospective, multicenter, randomized, quadruple-blind, placebo-controlled study. This study aims to estimate the safety and efficacy of intravenous tranexamic acid (TXA) combined with intensive blood pressure lowering in ultra-early spontaneous intracerebral hemorrhage (ICH).

Study Overview

• Status: Not yet recruiting
• Conditions: Hypertension; Spontaneous Intracranial Hemorrhage
• Intervention / Treatment: Drug: intravenous tranexamic acid (TXA) infusion; Drug: Placebo

Detailed Description

This trial is designed to evaluate whether tranexamic acid can reduce hematoma expansion and improve functional outcomes when combined with intensive blood pressure lowering in cases of ultra-early intracerebral hemorrhage with a high risk of hematoma expansion.

Participants who meet the eligibility criteria will be randomly assigned in a 1:1 ratio to either the TXA therapy group or the placebo control group. The initial infusion of 1 g of TXA or a matching placebo, along with intensive blood pressure lowering treatment, should commence as quickly as possible, ideally within 30 minutes of randomization. Following this, an additional 1 gram of TXA or a corresponding placebo will be administered via continuous intravenous infusion over 8 hours. Both groups will receive intensive blood pressure management during the first 24 hours after the onset of symptoms. Participants will be followed for 90 days after randomization for efficacy and safety outcomes.

• Study Type: Interventional
• Enrollment (Estimated): 532
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Jialu Li, MD; Phone Number: 86-176-0074-2526; Email: lijialu@ccmu.edu.cn
• Study Contact Backup: Name: Xiuhai Guo, MD, PhD; Phone Number: 86-10-83198852; Email: guoxhxuan@126.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100053
      • Xuanwu Hospital, Capital Medical University
      • Contact: Xiuhai Guo, MD, PhD; Phone Number: 86-10-83198852; Email: guoxhxuan@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age between 18 to 80 years old;
2. A definite diagnosis of supratentorial brain parenchymal hemorrhage by non-contrast cranial CT scan;
3. Hemorrhage volume less than 40 mL, as calculated using the ABC/2 method, with ultra-early hemorrhage growth (uHG) 10 mL/h or higher;
4. A clear time of symptom onset, and the randomization must occur within 2 hours from the onset;
5. At least two measurements of systolic blood pressure that are ≥150 mmHg and <220 mmHg, with at least a 2-minute interval between measurements.;
6. Baseline NIHSS of 8 or higher, or unilateral limb muscle strength of 0-3 grades;
7. GCS score greater than 8;
8. The patient or their legal representative has signed an informed consent form.

Exclusion Criteria:

1. Pre-illness mRS > 2;
2. Primary thalamic hemorrhage or intracerebral hemorrhage that has extended into the ventricles;
3. Scheduled for surgical intervention (i.e., hematoma evacuation, craniectomy);
4. Secondary ICH from tumors, AVMs, and aneurysms;
5. Traumatic brain injury-related hemorrhage;
6. Recent stroke, TIA, or thrombolytic therapy;
7. On anticoagulants;
8. Blood disorders, platelets <50,000/µL, or INR ≥1.8;
9. Antihypertensive therapy contraindications;
10. Indications for immediate blood pressure reduction;
11. Active thrombosis or thromboembolic history;
12. Hereditary or acquired thrombophilia;
13. Acquired color vision deficiency;
14. Epilepsy history;
15. GFR <90 mL/min;
16. Elevated ALT or liver disease;
17. Allergy to TXA or antifibrinolytics;
18. Life expectancy <12 months;
19. Pregnant or lactating women;
20. In other interventional clinical trials;
21. Other investigator-defined ineligibilities.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tranexamic acid (TXA) group; Intravenous tranexamic acid 1 g over 10 minutes, followed by 1 g over 8 hours, with intensive blood pressure lowering.	Drug: intravenous tranexamic acid (TXA) infusion; Intravenous tranexamic acid will be administered as an initial dose of 1 g (10mL: 1g, diluted in 90 mL normal saline) over 10 minutes, followed by a maintenance dose of 1 g over 8 hours (10mL: 1g, diluted in 240 mL normal saline). Intensive blood pressure lowering will be maintained throughout the treatment period until 24 hours after onset.
Placebo Comparator: Control group; An intravenous placebo (normal saline) over 10 minutes, followed by another continuous infusion of placebo over 8 hours, with intensive blood pressure lowering maintained.	Drug: Placebo; An intravenous placebo (10mL NS, diluted in 90mL NS) matching the specification and appearance of TXA will be administered as an initial bolus over 10 minutes, followed by a continuous infusion of placebo (10mL NS, diluted in 240mL NS) over 8 hours, with intensive blood pressure lowering maintained throughout the treatment period and continued until 24 hours after symptoms onset.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
modified Rankin Scale (mRS) of 0-3 at 90 days	90 ± 7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hematoma expansion at 24 hours	The expansion is defined as a 33% or 6 mL increase from baseline hematoma volume or develop an intraventricular hemorrhage.	24±3 hours
Absolute intracerebral haematoma growth at 24 hours		24±3 hours
Relative intracerebral haematoma growth at 24 hours		24±3 hours
Intraventricular hematoma (IVH) growth at 24 hours		24±3 hours
National Institutes of Health Stroke Scale (NIHSS) score at 24 hours		24±3 hours
Neurologic deterioration in first 24 hours	Neurologic deterioration is defined as an increase of 4 or more points on the National Institutes of Health Stroke Scale (NIHSS) from baseline to 24 hours, or a decline of 2 or more points on the Glasgow Coma Scale (GCS).	24±3 hours
Received surgical intervention within 7 days	Interventions include hematoma evacuation, external ventricular drainage, and craniectomy.	Within 7±3 days
modified Rankin Scale (mRS) score at 90 days		90±7 days
modified Rankin Scale (mRS) score of 0-4 at 90 days		90±7 days
Utility weighted modified Rankin Scale (mRS) score at 90 days		90±7 days
Major thromboembolic events	This includes ischemic stroke, myocardial infarction, and pulmonary embolism.	Within 90±7 days
Death due to any cause within 90 days		Within 90±7 days
Severe hypotension	Hypotension with clinical consequences (including acute renal failure) that required corrective therapy with intravenous fluids, vasopressors, or hemodialysis.	Within 72 hours

Collaborators and Investigators

• Sponsor: Xuanwu Hospital, Beijing
• Collaborators: Wuzhou Red Cross Hospital; The People's Hospital of Liaoning Province; Hunan Provincial People's Hospital; Capital Medical University; Huizhou Third People's Hospital, Guangzhou Medical University; Linyi People's Hospital; Peking University Care Luzhong Hospital; The First Affiliated Hospital of Hebei North University; The First People's Hospital of Qujing, Yunnan Province; Beijing Municipal Health Commission; Jiaozuo Tumor Hospital; Suzhou First People's Hospital; Yantai Penglai Traditional Chinese Medicine Hospital; Beijing Aerospace Center Hospital; Xing'anmeng People's Hospital; Nanyang Nanshi Hospital, Henan University
• Investigators: Principal Investigator: Xiuhai Guo, MD, PhD, Xuanwu Hospital, Beijing

Study record dates

Study Major Dates

• Study Start (Estimated): December 31, 2024
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: December 30, 2024
• First Submitted That Met QC Criteria: December 30, 2024
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 5, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Tranexamic acid; Intracranial Hemorrhage; Intensive blood pressure lowering; Haemostatic therapy
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Hemorrhage; Cerebral Hemorrhage; Intracranial Hemorrhages; Molecular Mechanisms of Pharmacological Action; Antifibrinolytic Agents; Fibrin Modulating Agents; Hemostatics; Coagulants; Tranexamic Acid
• Other Study ID Numbers: TIME-ICH

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No